Cervical Cancer
Conditions
Keywords
Cervical Cancer, Chemotherapy, Paclitaxel, Carboplatin, Cisplatin, Radiotherapy, Chemoradiation, Brachytherapy, Stage IB2 Cervical Cancer, Stage IIA Cervical Cancer, Stage IIB Cervical Cancer, Stage IIIB Cervical Cancer, Stage IVA Cervical Cancer
Brief summary
Chemoradiation has been the standard treatment for advanced cervical cancer for a decade, but one third of women still die from a failure to control systemic disease. In a recent multicentre phase II trial of 46 women the investigators found that, 68% of women had tumours that responded to weekly induction chemotherapy prior to chemoradiation. The induction chemotherapy had acceptable toxicity and did not compromise the standard chemoradiation treatment. In addition, the overall survival and progression free survival at 3 years was 66% (95% CI 4779). These results, together with acceptable toxicity, provide justification for evaluating induction chemotherapy prior to chemoradiation in a randomised phase III trial. The investigators aim to investigate in a randomised trial whether additional induction chemotherapy given on a weekly schedule immediately before standard chemoradiation leads to an improvement in overall survival. The investigators plan to recruit 770 women with locally advanced cervical cancer who are eligible for standard chemoradiation, they will be randomised to weekly carboplatin and paclitaxel chemotherapy for 6 weeks followed by chemoradiation or to chemoradiation alone. The trial will recruit for 4 years with 5 years of follow up period.
Interventions
DRUGPaclitaxel
Paclitaxel 80 mg/m2 (capped at 162mg maximum total dose) weekly for 6 weeks i.e. on days 1, 8, 15, 22, 29 & 36.
DRUGCarboplatin
Carboplatin AUC 2 (capped at 270mg maximum total dose) weekly for 6 weeks i.e. on day 1, 8, 15, 22, 29, & 36.
RADIATIONRadiotherapy
Radiotherapy comprising external beam 40-50.4Gy in 20-28 fractions plus intracavity brachytherapy to achieve a minimum total EQD2 dose of 78-86Gy.
DRUGCisplatin
Cisplatin 40 mg/m2 (capped at 70mg total dose) weekly for five weeks maximum, commencing in the first week of radiotherapy or as soon as blood counts have recovered from induction chemotherapy.
Sponsors
Cancer Research UK
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed FIGO stage Ib2-IVa squamous, adeno or adenosquamous carcinoma of the cervix (except FIGO IIIA). Patients with histologically confirmed FIGO stage IB1 and positive lymph nodes are also eligible * Deemed suitable and fit for radical chemoradiation * Medically fit to receive carboplatin and paclitaxel * ECOG performance status 0 - 1 * No evidence of active TB * Aged 18 and over * Adequate renal function, defined as a GFR ≥ 60 ml/min calculated using the Wright equation (or ≥ 50 ml/min for radioisotope GFR assessment) * Adequate liver function, as defined by ALT or AST \< 2.5 ULN and bilirubin \< 1.25 ULN * Adequate bone marrow function as defined by ANC ≥1.5 x 109/L, platelets ≥ 100 x 109/L * Using adequate contraception precautions if relevant * A documented negative HIV test (patients recruited from high risk countries or who have moved within the past 10 years from high risk countries) * A documented negative pregnancy test (if applicable) * Capable of providing written or witnessed informed consent Patients with positive (pelvic/para-aortic/both) nodes (either histologically/PET positive ≥15 mm on CT/MRI) at or below the level of the aortic bifurcation may be included in the study provided none of the
Exclusion criteria
apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival | 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival | 12 weeks post treatment and then as required |
| Adverse events (AE) as assessed by the Common Terminology Criteria for Adverse Events v4.03 | To be assessed at every timepoint i.e. baseline; at every chemotherapy cycle, at all follow up visits. |
| Quality of Life (UK and Ireland only) as assessed by EORTC QLQ-C30, QLQ-CX24 and EQ-5D | Baseline, during induction chemotherapy (Week 4), day 1 of chemoradiation, during chemoradiation (Weeks 3), 4 weeks post end of treatment, and as part of follow up (3 monthly for 2 years; 6 monthly for 3 years until 5 years post randomisation) |
| Patterns of first relapse (local and/or systemic) | 12 weeks post treatment and as required |
Countries
Brazil, India, Italy, Mexico, United Kingdom
Outcome results
None listed